18β-Glycyrrhetinic
acid (18Gly), the major bioactive component of Glycyrrhizae Radix, possesses anti-ulcerative, anti-inflammatory, and other pharmacological properties. Although 18Gly is associated with immunoregulatory functions of allergic diseases, the pathophysiological mechanisms of 18Gly action in allergic inflammatory
lung disease have not been examined. Moreover, there are no in vivo studies on the
anti-asthmatic effects of 18Gly in allergic
asthma. We investigated its effect and mechanism of action in airway
inflammation in a BALB/c mouse model of allergic
asthma. Interestingly, 18Gly strongly suppressed
airway hyperresponsiveness, accumulation of inflammatory cells, and levels of T helper type 2 (Th2)
cytokines (
interleukin (IL)-5 and
IL-13) in bronchoalveolar lavage fluid (BALF). It also attenuated lung
IL-5,
IL-13, and
IL-4 expression, but it upregulated
peroxisome proliferator-activated receptor gamma (PPARγ)
mRNA expression in lungs. Moreover, it exerted immunomodulatory effects by suppressing Th2
cytokines (IL-5, IL-13) production through upregulation of forkhead box p3 (Foxp3), and downregulation of signal transducer and activator of transcription (STAT6), GATA-
binding protein 3 (GATA-3), and
retinoic acid-related orphan receptor γ t (RORγt) expression. These results suggest that the
anti-asthmatic activity of 18Gly may occur by the suppression of
IL-5,
IL-13, and OVA-specific
Immunoglobulin E (
IgE) production through inhibition of the RORγt, STAT6, GATA-3 pathways and upregulation of the Foxp3 transcription pathway. Also, 18Gly treatment was protective against the oxidative stress by inducing significant decrease of
reactive oxygen species (ROS) generation in MH-S alveolar macrophage cells. Our results suggest that 18Gly can improve allergic
asthma and can be a novel therapeutic component for the treatment of allergic
asthma.